ABSTRACT The Genetic Disorders of Mucociliary Clearance Consortium consists of eight geographically diverse clinical research sites across North America that collectively study inherited respiratory diseases related to impaired mucociliary clearance and airway host defense, resulting in chronic suppurative respiratory diseases. The Con- sortium has made remarkable progress advancing clinical practice, developing diagnostic tests and validating various clinical outcome measures for primary ciliary dyskinesia. In addition, the Consortium was pivotal to the identification and characterization of 40 primary ciliary dyskinesia-associated genes, which has provided insights into disease pathophysiology and uncovered genotype-phenotype relationships. Through these investigations, we have recently identified subjects who have confirmed or probable diagnosis of primary immunodeficiencies. By systematically evaluating patients, coupled with genetic testing, we expect to determine the molecular diag- nosis in patients with chronic suppurative respiratory disease. The overarching goal of this multidisciplinary proposal is to determine the genetic bases, pathophysiology and clinical manifestations of rare, chronic suppurative respiratory diseases; improve diagnostic capabilities; and identify novel therapeutic targets and endpoints for clinical trials that will ultimately improve outcomes for affected individuals. The program includes three distinct but thematically-linked projects. The first project is a cross-sec- tional study defining the genetic and pathophysiological bases of chronic suppurative lung disease and bronchi- ectasis, concentrating on primary ciliary dyskinesia and primary immunodeficiencies. Second, we will initiate a longitudinal study to assess the effect of respiratory exacerbations on disease progression in patients with pri- mary ciliary dyskinesia. Finally, the third project is a cross-sectional study characterizing the clinical impact of upper airway and ear disease in primary ciliary dyskinesia and primary immunodeficiencies. The Consortium will also develop pilot and feasibility projects that will yield novel approaches to diagnosing primary ciliary dyskinesia and primary immunodeficiencies, provide insights into pathogenesis of rare suppura- tive lung diseases, and test novel outcome measures critical for clinical trial readiness. The Consortium will support early-career investigators involved in rare disease research through the Career Enhancement Core, providing training, workshops, and exchanges across consortia. In addition, we will develop unique educational programs with professional societies and research collaboratives worldwide. Ultimately, we expect the Consortium's efforts will greatly advance our understanding of genetics, pathophysiol- ogy, clinical manifestations, and the natural history of various chronic suppurative respiratory diseases, improve diagnostic tools and management, and yield novel therapeutic targets and endpoints for clinical trials.